This proposal is designed to develop and test several new approaches to the total synthesis of a wide variety of medicinally active natural products. The target molecules vary greatly in their structural complexity, ranging from the complex pentacyclic alkaloids (morphine, codeine, reserpine, and herquline) and tetracyclic steriods (cortisone, estrone) and bionans (desmethyl epipodophyllotoxin) to the simple bicyclic alkaloid slaframine. The key step of all of the synthetic approaches is an intramolecular reaction or rearrangement which requires, by the intramolecularity of the process, the formation of the stereochemically desired isomer in preference to all others. The intramolecular processes used in these syntheses are Diels-Alder reations, [3,3]-sigmatropic shifts, and nucleophilic additions (Michael additions or additions to immonium salts). In all cases, the syntheses are designed so as to be quite short (9 steps to morphine, 7 steps to estrone, etc.) and general enough so that many other structurally related systems could be formed quite easily. The principles developed in these synthese - e.g., formation of quaternary centers via an oxy-Cope rearrangement, steric control of the stereochemistry of internal cycloadditions, the facile generation and cyclization of 1-azabutadienes, among others - would be applicable and of great value to organic synthesis in general. Because of the extreme shortness of the syntheses, the importance of the targets, and the high intrinsic value of the methods themselves, the likelihood of an important contribution to chemistry is quite high.